Trastuzumab plus pertuzumab yielded an 18% objective response rate and left ventricular systolic dysfunction in 6 of 11 patients with trastuzumab-insensitive HER2-positive metastatic breast cancer.
Does the combination of trastuzumab and pertuzumab cause cardiac toxicity and provide efficacy in patients with trastuzumab-insensitive HER2-positive metastatic breast cancer?
The combination of trastuzumab and pertuzumab in trastuzumab-pretreated HER2-positive metastatic breast cancer provides modest clinical benefit but is associated with frequent, albeit mostly asymptomatic, left ventricular systolic dysfunction.
PURPOSE: To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy. EXPERIMENTAL DESIGN: Patients with measurable HER2(+) metastatic breast cancer, or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v. followed by 6 mg/kg trastuzumab and 420 mg pertuzumab every 3 weeks. Cardiac evaluation and tumor response were assessed every 3 and 6 weeks, respectively. RESULTS: Eleven patients received 64 cycles of trastuzumab plus pertuzumab. A total of 92 echocardiograms and 8 cardiac magnetic resonance imaging studies were done. With the lower limit of normal LVEF 55%, left ventricular systolic dysfunction was observed in six patients, three grade 1, two grade 2, and one grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The objective response rate was 18%. Two patients had partial responses, three had stable disease, and six had progressive disease. The median time to progression was 6 weeks. In baseline tumors from formalin-fixed paraffin-embedded primary and/or metastatic tumor biopsies, pHER2-Y1248 trended toward an increase in patients with partial response compared with those with stable disease/progressive disease (P = 0.095). CONCLUSION: Trastuzumab plus pertuzumab may have clinical benefit in selected patients who have previously been treated with trastuzumab. Cardiac toxicity, although asymptomatic in most cases, was associated with this treatment. Further evaluation of efficacy of this combination is required to define the overall risks and benefits.
Portera et al. (Thu,) conducted a other in HER2-positive metastatic breast cancer (n=11). Trastuzumab plus pertuzumab was evaluated on Objective response rate. Trastuzumab plus pertuzumab yielded an 18% objective response rate and left ventricular systolic dysfunction in 6 of 11 patients with trastuzumab-insensitive HER2-positive metastatic breast cancer.